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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Antimicrobials, Resistance and Chemotherapy

Transcriptomics and network pharmacology reveal the molecular mechanisms through which leonurine protects against Salmonella enteritidis infection in IEC-6 cells

Provisionally accepted
Chenghui  XuChenghui Xu1Li  YangLi Yang1*Jie  WeiJie Wei2Ruixue  SaRuixue Sa1Yuanyuan  YuanYuanyuan Yuan1Xia  LiningXia Lining1Huijun  ShiHuijun Shi1Qiang  FuQiang Fu1
  • 1College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China, Urumqi, China
  • 2Xinjiang Academy of Animal Sciences Institute of Veterinary Medicine, Urumqi, China

The final, formatted version of the article will be published soon.

Leonurine has been demonstrated to exert significant therapeutic effects against Salmonella enteritidis induced intestinal inflammation; however, its precise mechanism of action in combating Salmonella infection remains unclear. In this study, a Salmonella infection IEC6 cell model was established to evaluate the efficacy of leonurine in combating Salmonella infection using CCK8, cytopathic effect (CPE) analysis, immunofluorescence, transmission electron microscopy (TEM), and flow cytometry. Subsequent integration of network pharmacology, transcriptomics, and molecular docking revealed potential targets and signalling pathways, which were further validated by RT‒qPCR and Western blotting. Immunofluorescence and TEM revealed that leonurine effectively inhibited bacterial invasion and intracellular proliferation. Flow cytometry and CPE assays demonstrated its ability to alleviate cellular damage and inhibit apoptosis. The integrated network pharmacology transcriptomics molecular docking analysis revealed robust interactions between leonurine and PTGS2, PARP1, and mTOR. Mechanistic validation confirmed that leonurine inhibits Salmonella invasion via the modulation of tight junction proteins and restricts intracellular bacterial proliferation by regulating ferroptosis and autophagy signalling pathways. This study reveals the potential targets and molecular mechanisms through which leonurine combats Salmonella infection, providing a scientific foundation for the prevention and control of salmonellosis.

Keywords: Leonurine, Salmonella enteritidis, invasion, Mechanism, Transcriptomics, Network Pharmacology, IEC-6 cells

Received: 17 Jul 2025; Accepted: 13 Nov 2025.

Copyright: © 2025 Xu, Yang, Wei, Sa, Yuan, Lining, Shi and Fu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Li Yang, yl@xjau.edu.cn

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